Ulcerating diseases of the gastrointestinal tract, commonly referred to as peptic ulcers, are diseases in which there is a defect in the epithelium of the gastrointestinal tract. This type of defect usually occurs through the combined action of hydrochloric acid and pepsin. By definition, peptic ulcers penetrate to at least the submucosa; more superficial lesions are referred to as erosions. Peptic ulcers may occur in many locations of the gastrointestinal tract including the stomach, duodenum or esophagus, in Meckel's diverticulum, at the sight of a surgically created anastomosis, and, rarely, in the upper jejunum.
Twenty years ago, treatment of peptic ulceration consisted of bedrest, a bland diet, antacids, and/or surgical removal of the affected area. More recently, H.sub.2 -receptor antagonists have been used in the treatment of peptic ulcers. The two most commonly used H.sub.2 -receptor antagonists are ranitidine and cimetidine, both of which act therapeutically by inhibiting gastric acid secretion. The effectiveness and unwanted effects of these two antagonists has been extensively studied, e.g. by Thomas et al., in Clinics in Gastroenterology. Volume 13, Number 2, at pages 501-529.
While treatment with these antagonists has been widespread and relatively successful, many peptic ulcers do not respond to H.sub.2 -receptor antagonist therapy. For example, while the reasons are not clearly understood, some 20 to 30% of duodenal ulcers do not heal after four to six weeks of therapy with either cimetidine or ranitidine. Moreover, recurrence or relapse of the ulcerating condition is not uncommon with H.sub.2 -receptor antagonists.
Sucralfate has also been used as an ulcer curative agent with minimal side effects. Sucralfate is believed to influence multiple mechanisms of gastrointestinal protection and repairing/healing including i) adsorption of pepsin and bile acids, ii) cytoprotective activity of the gastro stimulation of mucus secretion and bicarbonate secretion by the gastric mucosa, iii) protection against damage to the prolifactive zone, and iv) protection of vascular integrity. Although major advances have been made in the understanding of how sucralfate prevents erosions and ulcers, and how it accelerates the healing of ulcers, a major gap exist in the elucidation of chronic therapeutic actions of this drug.
Fibroblast growth factor (FGF), has been shown to be a potent angiogenic factor which, inter alia. is responsible for neovascularization in wound healing. There are two types of FGF, acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). aFGF and bFGF are, however, acid and/or heat labile. Thus, the use of FGF in acid and/or heat environments such as in the treatment of peptic ulcers requires that it be stabilized to that environment in order to maximize its therapeutic value.
Recently, however, in PCT application serial no.: PCT/U.S. Pat. No. 8,903,467, published Mar. 8, 1990, the disclosure which is hereby incorporated by reference, there is disclosed certain acid-resistant FGF compositions including recombinant FGF in combination with i) stabilizing agents such as glycosaminoglycan, glucan sulfates and sulfated cyclodextrins, ii) antisecretory agents such as H.sub.2 -receptor antagonists, iii) cytoprotective agents, and iv) antacids. These novel compositions are disclosed as being extremely effective in the treatment of ailments in which FGF would be a potent medicament but for the acid and/or heat environment to which it is subjected.
There continues to be a need, however, for new ways of further stabilizing FGF so that its diagnostic potential and therapeutic potential in the treatment of gastrointestinal conditions, wounds, and the like can be realized.